Key Points
- In the phase 3 SCOUT-HCM trial, mavacamten significantly reduced Valsalva LVOT gradient versus placebo in symptomatic adolescents with obstructive hypertrophic cardiomyopathy.
- Mavacamten was associated with broad improvements in obstruction severity, cardiac structure, and functional status.
- Safety findings were similar between mavacamten and placebo, with no deaths and no patients experiencing LVEF <50%.
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease, and pediatric-onset disease is associated with a worse prognosis than adult-onset HCM. In adolescents with obstructive disease, left ventricular outflow tract (LVOT) obstruction contributes to symptoms, functional limitation, and progression to advanced therapies. Despite this, no targeted pharmacologic therapies have been established in this population.
On March 29, 2026, at the American College of Cardiology Scientific Sessions, Dr. Joseph Rossano presented results from SCOUT-HCM (NCT06253221), a phase 3, randomized, double-blind, placebo-controlled trial evaluating mavacamten in adolescents aged 12 to <18 years with symptomatic obstructive HCM. The study was simultaneously published in the New England Journal of Medicine.
A total of 44 patients with Valsalva LVOT gradient ≥30 mm Hg, maximal LVOT gradient ≥50 mm Hg, LVEF ≥60%, and NYHA class II-III symptoms were randomized 1:1 to mavacamten or placebo. Baseline characteristics were balanced between groups. At 28 weeks, mavacamten significantly reduced Valsalva LVOT gradient compared with placebo, with a mean reduction sufficient to bring average gradients below the threshold for obstruction in the treatment group, while gradients remained elevated in the placebo group.
Secondary analyses demonstrated consistent improvements across multiple measures of disease severity. Mavacamten reduced resting and post-exercise LVOT gradients and was associated with improvements in diastolic function, left ventricular hypertrophy, NYHA functional class, and mitral regurgitation severity. A greater proportion of patients treated with mavacamten achieved clinically meaningful reductions in LVOT gradient and improvements in functional class compared with placebo. Exploratory analyses showed reductions in biomarkers of myocardial stress and injury, including NT-proBNP and high-sensitivity troponin, supporting a favorable biologic effect on disease activity. Safety outcomes were similar between treatment groups. Treatment-emergent adverse events and serious adverse events occurred at comparable rates in the mavacamten and placebo arms. No deaths occurred, and no patients experienced a reduction in LVEF below 50%, with no signals for atrial fibrillation or symptomatic heart failure observed during the study period.
Taken together, these findings demonstrate that mavacamten significantly improves LVOT obstruction and multiple markers of disease severity in adolescents with symptomatic obstructive HCM. The authors conclude that “SCOUT-HCM supports the use of mavacamten as an efficacious treatment option for symptomatic obstructive HCM in carefully selected adolescent patients, with long-term follow-up ongoing.”